miR-410与多种肿瘤发生发展、转移等密切相关。我们前期发现，miR-410在肺癌癌组织中高表达，并促进细胞增殖和转移，其可能机制为靶向抑制Gsk3β并激活Wnt/β-catenin信号通路，且其表达与癌组织分化程度呈负相关。虽然miR-410在肿瘤中的研究越来越多，但是对其在肺癌中异常高表达的机制仍不清楚。circRNAs作为一类新非编码RNA，通过结合miRNA调节下游靶基因发挥重要作用。我们研究发现，hsa_circ_0001085可能靶向结合miR-410，且在肺癌组织的表达趋势与miR-410相反。据此，我们推测hsa_circ_0001085在肺癌中可能通过结合miR-410调节靶基因Gsk3β表达来发挥作用。本课题将首次从circRNA层面揭示miR-410异常高表达的原因以及通过hsa_circ_0001085/miR-410/Gsk3β信号网络调节肺癌生长及转移的新机制

Studies have confirmed that miR-410 is related to tumor development, metastasis, drug resistance, diagnostic markers, prognosis and patient survival time, and can exert the role of tumor suppressor genes or oncogenes through influencing tumor cell proliferation, apoptosis, invasion and migration, angiogenesis, chemotherapy resistance, radiotherapy toxicity, cell metabolism and other processes. In lung cancer, our previous study found that miR-410 was highly expressed in patient cancer tissues, promoting cell proliferation and metastasis, which may be regulated by targeted inhibition of Gsk3β and activation of Wnt/β-catenin signaling pathway, and its expression level was negatively correlated with the degree of differentiation of patient. Although the role and mechanism of miR-410 in various tumors are increasingly studied, the role and mechanism of miR-410 in lung cancer are still poorly understood. CircRNAs, as a class of newly discovered non-coding RNAs, play an important role in various diseases mainly by binding miRNAs to regulate the functions of downstream target genes.Our further study found that hsa_circ_0001085 may bind with miR-410, and the expression of hsa_circ_0001085 in lung cancer tissues was opposite to that of miR-410.Therefore, we speculated that hsa_circ_0001085 may play an important role in lung cancer by targeting miR-410 to regulate the expression of downstream target gene Gsk3β. Herein, this study will, for the first time, apply luciferase assay, RIP, FISH, immunofluorescence, Western blot, immunohistochemistry, TUNEL, cell proliferation, apoptosis, cell cycle, clonal formation, nude mouse subcutaneous transplantation tumor model and other experimental techniques, from the circRNA level to reveal a new mechanism that hsa_circ_0001085 regulates miR-410 function through hsa_circ_0001085/miR-410/Gsk3β signaling axis in lung cancer, so as to provide more experimental evidences for miR-410 as a new target for lung cancer treatment.